Metformin Effective for Treating Teens With PCOS

TORONTO — Metformin appears to be an effective treatment in adolescents with polycystic ovary syndrome, Dr. Kenneth L. Jones reported at the annual meeting of the Endocrine Society.

His unfunded pilot study of the insulin-sensitizing agent in six affected teens showed that the drug restored menstrual regularity reduced high serum insulin and androgen levels, resulted in weight loss and reduction in body mass index, and improved hirsutism and acanthosis nigricans.

“We think this is a good way to go. And from what we know about a recent national study of metformin in type 2 diabetes, this is a safe drug in children,” declared Dr. Jones, professor of pediatrics and chief of pediatric endocrinology at the University of California, San Diego.

His small study drew particular interest at the meeting because of growing physician concern over the burgeoning increase in polycystic ovary syndrome (PCOS) and the related problem of type 2 diabetes in American adolescents.

Metformin recently received Food and Drug Administration approval for use in children with type 2 diabetes.

The drug was already approved for type 2 diabetic adults. Additionally, a number of pediatric endocrinologists have been influenced by studies showing that metformin also is effective for the metabolic abnormalities associated with PCOS in adults.

“I can assure you that many of my colleagues are using metformin to treat PCOS in kids across the country,” Dr. Jones said.

In his study he treated patients just to the point of symptomatic relief. In some girls that required only 500 mg/day while others needed up to 2 g/day

Canadian endocrinologists noted that although metformin has been available to U.S. physicians for only a few years, it has been marketed in Canada and Western Europe for decades and is supported by a large body of reassuring safety data.

In other new findings on PCOS presented at the meeting:

* A susceptibility gene for PCOS appears to be located on chromosome 19 near the insulin receptor gene.

Further work is required to determine whether this is the insulin receptor gene itself, a gene that regulates insulin receptor activity, or something else entirely said Dr. Yaron Tomer of Mount Sinai School of Medicine, New York, who identified the gene marker by comparing the genetics of 85 PCOS patients and 87 controls.

Dr. Andrea Dunaif is part of a team that, independent of Dr. Tomer, also located a PCOS susceptibility gene close to the insulin receptor.

She stressed that PCOS is far too complex to be fully explained by a single mutation. The importance of the national epidemic of obesity as a contributing environmental factor can’t be overstated, added Dr. Dunaif, chief of the division of women’s health at Brigham and Women’s Hospital and director of the national center of excellence in women’s health at Harvard Medical School, Boston.

* Dr. Dunaif said her family studies have shown that roughly half of sisters of PCOS patients are themselves affected. But only half of affected sisters have the classic syndrome with irregular menstrual cycles and marked obesity. The other half have polycystic ovaries and elevated androgen levels but have normal cycles and are less obese.

* Even modest weight loss through outpatient dieting is difficult for PGOS patients; those who succeed can expect to see improvement in some but not all metabollc parameters, said Dr. Ann E. Taylor of Massachusetts General Hospital, Boston.

She reported on 22 obese PCOS patients randomized to 6 months on a diet with 40% of calories from fat and 40% from carbohydrates, or to a diet with 25% of calories from fat and 55% from carbohydrates. Only 14 women were able to complete even the first 3 months of dieting.

Dieters lost a mean of 20 pounds from a baseline weight of 239 pounds. Their total serum cholesterol declined by a mean of 15.5 mg/dL, their waist circumference diminished by 1.7 inches, and their insulin response to glucose improved. But serum testosterone elevations and other reproductive hormone abnormalities remained. Nor did their ovulation rate improve.

The diet-responsive aspects of the disease showed greater improvement in patients on the lower-fat/higher-carbohydrate diet. This finding runs contrary to advice widely available on PCOS Web sites, many of which advocate low-carbohydrate diets, she said.

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COPYRIGHT 2000 International Medical News Group
in association with The Gale Group and LookSmart. COPYRIGHT 2001 Gale Group
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